Inhibin A concentrations in the sera of young women during and after chemotherapy for lymphoma: correlation with ovarian toxicity.
OBJECTIVE
Inhibin A concentrations in serum may reflect the ovarian granulosa cell compartment. To characterize the correlation between ovarian function after gonadotoxic chemotherapy for Hodgkin's or non-Hodgkin's lymphoma in young women, the immunoreactive inhibin A concentrations in the sera of these patients was measured before, during, and after the gonadotoxic chemotherapy.


METHODS
A prospective clinical protocol was undertaken in 20 cycling women with lymphoma, aged 15-40 years. A monthly injection of depot D-TRP6-GnRH-a (Decapeptyl CR, Ferring) was administered from before starting the chemotherapy until its conclusion, up to a maximum of six monthly injections. Most of the patients were treated with the mustargen-oncovin-procarbazine-prednisone (MOPP)/actinomycin D-bleomycin-vincristine (ABV) chemotherapy combination; 13 with and 7 without radiotherapy. A hormonal profile [follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-beta-estradiol (E2), testosterone (T), progesterone (P4), insulin-like growth factor (IGF)-1, IGF-BP3, and prolactin (PRL)] was taken before starting the gonadotropin-releasing hormone agonist (GnRH-a)/chemotherapy co-treatment and monthly thereafter until resuming spontaneous ovulation and menstrual cyclicity. This group of prospectively treated lymphoma patients was compared with a control group of 22 regularly cycling women who had been treated with chemotherapy (mostly MOPP/ABV) with or without radiotherapy for Hodgkin's or non-Hodgkin's lymphoma. Inhibin A immunoactivity developed by Nigel Groome was measured by an enzyme-linked immunoadsorbent assay (ELISA) commercial kit (Serotec).


RESULTS
Whereas all but one (40 years of age) of the surviving patients in the GnRH-a/chemotherapy co-treatment group resumed spontaneous ovulation and menses within 6 months, only one half of the patients in the "control" group (chemotherapy without GnRH-a co-treatment) resumed ovarian function and regular cyclic activity (P < 0.05). The remaining 50% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by approximately one third of the patients resuming cyclic ovarian function, suggesting a reversible ovarian damage in a larger proportion of women than those experiencing POF. The inhibin A immunoactive concentrations decreased during the GnRH-a/chemotherapy co-treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared to low levels in menopausal women and those who had developed POF.


CONCLUSIONS
If these preliminary data are consistent in a larger group of patients, inhibin A concentration may serve as a prognostic factor for predicting the resumption of ovarian function, in addition to the levels of FSH, LH, and E2.
Blumenfeld
Z
Z
Rambam Medical Center, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Ritter
M
M
Shen-Orr
Z
Z
Shariki
K
K
Ben-Shahar
M
M
Haim
N
N
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000097:blood* / Q000188:drug therapy* / Q000532:radiotherapy; D006728:Hormones / Q000097:blood; D006801:Humans; D007265:Inhibins / Q000097:blood* / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000188:drug therapy* / Q000532:radiotherapy; D008466:Mechlorethamine / Q000008:administration & dosage; D010049:Ovarian Diseases / Q000097:blood* / Q000139:chemically induced*; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011446:Prospective Studies; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D006728:Hormones; D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D007265:Inhibins; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D011241:Prednisone